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Time-varying closed-loop modeling of circulatory control in sleep-disordered breathing

TIME-VARYING CLOSED-LOOP MODELING OF CIRCULATORY
CONTROL IN SLEEP-DISORDERED BREATHING
by
Jarree Chaicharn
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOMEDICAL ENGINEERING)
December 2007
Copyright 2007 Jarree Chaicharn

There is no "gold standard" technique to assess the sympathetic activity. The well-known, simple and cost-effective tool for noninvasive assessment of circulatory control is power spectral analysis of heat rate variability and blood pressure variability. However, these methods ignore the influence of respiration on R-R interval and systolic blood pressure power spectrum. A more precise separation of the effect of respiration and systolic blood to heart rate variability and noninvasive assessment of circulatory control using a minimal closed-loop modeling of circulatory control system was developed, and the effects of continuous positive airway pressure therapy on cardiovascular variability in adults with obstructive sleep apnea syndrome (OSAS) were successfully revealed.; In this research, in addition to the Laguerre functions, we have used the Meixner functions as another set of the basis functions. Moreover, an existing closed-loop minimal model of cardiovascular variability, modified to incorporate time-varying parameter changes, was used to estimate the transfer relations among respiration, beat-to-beat systolic blood pressure, surrogate cardiac output (ratio of pulse pressure to R-R interval) or cardiac output derived from impedance cardiography, and R-R interval to assess: 1) the cumulative effects of repetitive arousal on circulatory control in healthy young adults, 2) the function of circulatory control in pediatric OSAS, and in congenital central hypoventilation syndrome (CCHS). We hypothesized that the model parameters, respiratory sinus arrhythmia (RSA) gain, arterial baroreflex (ABR) gain and circulatory dynamics (CID) gain were the parasympathetic cardiac index, cardiac sympathetic index, and peripheral sympathetic index, respectively.; We found that under orthostatic stress and cold face test, controls in OSAS group and CCHS group reacted the same, RSA gain decreased under orthostatic stress but increased during cold face test, ABR gain decreased under orthostatic stress, and CID gain increased under orthostatic stress and cold face test. These findings confirm our hypothesis and suggest that model-based analysis of cardiovascular response to orthostatic stress and cold face stimulation is useful as a noninvasive tool for quantifying daytime autonomic dysfunction in CCHS and children with OSAS.; The significant increase in ABR gain following about 50 minutes of undisturbed sleep represents a decrease in the sympathetic activity. However, ABR gain remained unchanged following repetitive arousals of 30s, 1 minute, or 2 minutes. Therefore, we conclude that the cumulative effects of repetitive arousal lead to disrupt the normal sympathetic activity.; Moreover, we have revealed that 1) in wakeful resting pediatric OSAS the sympathetic tone elevated, the parasympathetic function remains normal, but cardiovascular sympathetic reactivity is impaired, and 2) in wakeful resting CCHS, sympathetic tone elevated and parasympathetic tone diminished, and the parasympathetic and cardiovascular sympathetic reactivity are partially impaired.

TIME-VARYING CLOSED-LOOP MODELING OF CIRCULATORY
CONTROL IN SLEEP-DISORDERED BREATHING
by
Jarree Chaicharn
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOMEDICAL ENGINEERING)
December 2007
Copyright 2007 Jarree Chaicharn